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    RESEARCH AND EDUCATION

    SECTION EDITOR

    LOUIS J. BOUC:HER

    Osseointegration and its experimental background

    Per-Ingvar Brinemark, M.D., Ph.D.*

    University of G6teborg and Institute for Applied Biotechnology, Gateborg, Sweden

    0

    sseointegration in clinical dentistry depends on an

    understanding o:f the healing and reparative capacities

    of hard and soft tissues. Its objective is a predictable

    tissue response to the placement of tooth root ana-

    logues. Such a response must be a highly differentiated

    one, and one that becomes organized according to

    functional dema:nds. Since 1952, we have studied the

    concept of tissue4ntegrated prostheses at the Laborato-

    ry of Vital Microscopy at the University of Lund, and

    subsequently at the Laboratory for Experimental Biol-

    ogy at the University of GGteborg. Our collaborators in

    this research have included representatives from medi-

    cal and dental faculties, various research institutes, and

    departments of technology. The basic aim has been to

    define limits for clinical implantation procedures that

    will allow bone and marrow tissues to heal fully and

    remain as such, rather than heal as a low differentiated

    scar tissue with unpredictable sequelae. The studies

    involved analyses of tissue injury and repair in diverse

    sites in different animals, with particular reference to

    microvascular structure and function. Special emphasis

    was placed on analyzing the disturbances caused in the

    intravascular rhelology of blood by means of a series of

    different methodological approaches. The objective of

    this article is a brief review of the various investiga-

    tions that have led to the clinical application of osseo-

    integration.

    CONCEPT DEVELOPMENT

    The initial concept of osseointegration stemmed

    from vital microscopic studies of the bone marrow of

    the rabbit fibula., which was uncovered for visual

    inspection in a modified intravital microscope at high

    resolution in accordance with a very gentle surgical

    preparation technique. With special instrumentation,

    the marrow could be studied in transillumination in

    vivo, and in situ, after the covering bone was ground

    Presented at the Toronto Conference on Osseointegration in Clinical

    Dentistry, Toronto, Ont., Canada, and the Academy of Denture

    Prosthetics, San Diego, Calif.

    *Professor and Head, Laboratory of Experimental Biology, Depart-

    ment of Anatomy.

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    down to a thickness of only 10 to 20 pm. Circulation

    was maintained in this thin layer of bone and with very

    few signs of microvascular damage, which is the

    earliest and most sensitive indication of tissue injury.

    These intravascular studies of bone marrow circulation

    also revealed the intimate circulatory connection

    among marrow, bone, and joint tissue compartments.

    Subsequent studies of the regeneration of bone and

    marrow emphasized the close functional connection

    between marrow and bone in the repair of bone

    defects.

    We, therefore, performed a series of in vivo studies

    on bone, marrow, and joint tissue with particular

    emphasis on tissue reaction to various kinds o f injury:

    mechanical, thermal, chemical, and rheologic. We were

    also concerned with the various therapeutic possibili-

    ties to minimize the effect of such trauma. Aiming at a

    restitution ad integrum, we further sought to identify

    additional traumatic factors such as wound disinfec-

    tants and to explore the development of procedures that

    promote predictable healing of differentiated tissues.

    We also performed long-term in vivo microscopic

    studies of bone and marrow response to implanted

    titanium chambers of a screw-shaped design. These

    studies in the early 1960s strongly suggested the

    possibility of osseointegration since the optical cham-

    bers could not be removed from the adjacent bone once

    they had healed in. W e observed that the titanium

    chambers were inseparably incorporated within the

    bone tissue, which actually grew into very thin spaces

    in the titanium. Interdisciplinary clinical cooperation

    with plastic surgeons and otolaryngologists enabled us

    to study the repair of mandibular defects and replace-

    ment of ossicles by means of autologous bone grafts.

    Desired anatomic shapes of bone grafts were pre-

    formed in rabbits and dogs and subsequently applied

    clinically with long-term follow-up. In an extensive

    series, the repair of major mandibular and tibia1 defects

    in dogs was studied. Various procedures were used,

    with the most successful being the one based on the

    prior integration of titanium fixtures on both sides of

    the defect to be created later. When the fixtures had

    become safely incorporated within the bone, a defect

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    Fig. 1. A, Schematic representation of experimental defects in mandible and tibia in

    dog that were reconstructed by means of autologous marrow and spongious bone grafts

    stabilized by titanium splints secured to osseointegrated fixtures in both sides of defect.

    B, Topography of lower leg in dog at time of resection of tibia. Two lateral tibia1

    stabilizers were used. Periosteum was completely removed in area of defect. C,

    Reconstructed tibia 3 years later with stabilizers removed. D, Radiograph illustrates

    anatomy of stabilizing-fixtures and splints.

    was created, the topographical relation between the cut

    edges was maintained by titanium splints, and the

    tissue defect was compensated for by an autologous

    graft of trabecular bone and marrow (Figs. 1 and 2).

    Separate studies were performed on the healing and

    anchorage stability of titanium tooth root implants or

    fixtures of various sizes and designs. We found that

    when such an implant was introduced into the marrow

    cavity, and following an adequate immobilized healing

    period, a shell of compact cortical bone was formed

    around the implant without any apparent soft tissue

    intervention between normal bone and the surface of

    the implant (Fig. 3).

    We observed a direct correlation among microtopo-

    graphy of the titanium surface, the absence of contam-

    ination, the preparatory handling of the bone site, and

    the histologic pattern elicited in the adjacent bone. In a

    separate study, fixtures were installed in the tail

    vertebrae of dogs with successful integration even when

    abutments were allowed to pierce through the skin.

    On the basis of the findings in these experimental

    studies, we decided to perform a series of experiments

    that would enable us to develop clinical reconstructive

    procedures for the treatment of major mandibular

    defects, including advanced edentulous states. It was

    felt that both osseointegration and autologous bone

    grafts would be useful in these clinical defect situa-

    tions.

    Teeth were extracted in dogs and replaced by

    osseointegrated screw-shaped titanium implants (Fig.

    4). Fixed prostheses were connected after an initial

    healing time of 3 to 4 months without loading (Fig. 5).

    In this manner, the fixtures were allowed to heal under

    a mucoperiosteal flap, which was then pierced for

    abutment connection and subsequent prosthetic treat-

    ment.

    The anterior teeth, including the canines, were

    usually retained and the premolars and first molars

    removed. Different types of prosthetic designs were

    used; we started with a design similar to the one used

    for complete dentures and ended up with a gold

    porcelain fixed prosthesis (Fig. 6). Radiologic and

    histologic analyses of the anchoring tissues showed that

    integration could be maintained for 10 years in dogs

    with maintained healthy bone tissue and without

    progressive inflammatory reactions.

    At the time the animals were killed, the titanium

    fixtures could not be removed from the host bone unless

    cut away. The anchorage capacity of the separate

    implants was determined as 100 kg in the lower jaw

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    Fig. 2. A, Experimental defect in dogs mandible reconstructed with stabilizing buccal

    antcl ingual titanium splints and autologous marrow and spongious bone graft anchored

    to integrated fixtures. B, Reconstructed area 6 months later.

    Fig. 3. A to C, Experimental titanium fixture incorporated in dogs tibia illustrating

    new bone formation around fixture in medullary cavity.

    and 30 to 50 kg in the upper jaw. Efforts to extract the

    implants led to fractures in the jaw bone per se, not at

    the actual interface.

    Microradiographic analyses

    revealed load-related remodeling of the jaw bone

    around the implant, even in those cases where the

    implants were in very close proximity to the nasal and

    sinus mucoperiosteum at installation.

    In order to reconstruct severely resorbed edentulous

    jaws, we developed a special grafting procedure. It was

    based on preformation of the graft at the donor s ite to

    the desired anatomy. At the same time, we integrated

    fixtures in the graft-to-be. The bone graft was made

    to adapt to the required anatomy within a titanium

    mold. Donor sites were tibiae and ribs of rabbits and

    dogs.

    These long-term experimental studies suggested the

    possibility of achieving and maintaining bone anchor-

    age under unlimited loading of dental prostheses in the

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    Fig. 4. A, In first experimental studies, a combination of subperiosteal and transosseous

    titanium implants was used. This was found to provide anchorage but also uncontrolled

    soft tissue reactions. Therefore, separate screw-shaped titanium fixtures were developed,

    B, which were finally designed after experimental evaluation of about 50 different types

    of implants.

    Fig. 5. Diagrammatic representation of main steps and procedures for anchorage of a

    prosthesis to osseointegrated jaw bone fixtures. A, Preoperative situation. B, Fixture

    installed and covered by mucoperiosteal tissues. C, Abutment connected to fixture after a

    healing period. D and E, Prosthesis attached to abutment.

    dog attached to osseointegrated fixtures. Soft tissue

    penetration of titanium abutments could be used with-

    out untoward reactions in edentulous jaws, and also for

    the attachment oftitanium chambers for vital micros-

    copy in rabbit and dog tibiae.

    We carried out vital microscopic studies on human

    microcirculation and intravascular behavior of blood

    cells at high resolution by means of an implanted

    optical titanium chamber in a twin-pedicled skin tube

    on the inside of the left upper arm of healthy volun-

    teers. The tissue reaction as revealed by intravascular

    rheologic phenomena was studied in long-term experi-

    ments in these chambers without indications of inflam-

    matory processes. It, therefore, seemed reasonable to

    assume that bone anchorage according to the principle

    of osseointegration might also work in humans, and we

    treated our first edentulous patients in 1965.

    In those edentulous jaws where the remaining bone

    was inadequate for fixture anchorage, a composite

    reconstruction procedure was developed.

    A procedure of preformation was applied with the

    proximal metaphysis of the tibia used as the donor site.

    The combination of preformed grafts with integrated

    fixtures prov ided good long-term clinical results.

    Immediate autologous bone and marrow grafts are now

    being tried; and our longitudinal experiences indicate

    that with an extremely careful prosthodontic proce-

    dure, immediate bone grafts can also provide good

    long-term results. They have the advantage of requir-

    ing only one major surgical procedure as compared to

    two for the preformed graft, but the disadvantage of

    less predictable survival of the grafted bone.

    In those patients in whom the loss of jaw bone is not

    limited to the alveolus but also includes a discontinuity

    of the jaw bone, a preformed autologous bone graft

    from the iliac bone has been used and has provided

    good, predictable, long-term results. In accordance

    with the same basic principle as for preformed alveolar

    bone grafts, the desired graft is prepared in the iliac

    bone with a few connections left to the compact bone

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    OSSEOINTEGRATION

    Fig. 6. A, Edentulous upper and lower jaw in a dog with three fixtures integrated in

    each jaw. B, An acrylic resin prosthesis. C, A chrome-cobalt superstructure. D, Two

    fix,tures support a prosthesis made of porcelain baked to metal with molar tooth as a

    cantilevered abutment.

    and the marrow tissue. The graft-to-be is partly

    surrounded by a. titanium mold and a titanium foil.

    Fixtures are installed in two directions to produce

    anchorage for a splint connecting the graft to the

    remaining part of the mandible and to provide anchor-

    age for a fixed partial denture. Clinical long-term

    follow-up has shown that the grafted bone remains in

    its prepared shape even in the articular region.

    OSSEOINTEGRATION IN

    CLINICAL DENTISTRY

    The edentulous jaw is a typical example of a tissue

    defect that causes different degrees of functional distur-

    bances. A well-fitting denture appears to be an accept-

    able alternative to natural teeth as long as the anatomy

    of the residual hard and soft tissues provides good

    retention for the prosthesis. Progressive loss of alveolar

    bone tends to undermine the relative stability of the

    denture and can create severe problems of both a

    functional and psychosocial nature (Fig. 7).

    Different procedures have been advocated to anchor

    dental prostheses in the soft or hard tissues of the

    edentulous mouth. However, long-term clinical follow-

    ups indicate that such procedures do not provide

    predictable and good long-term function. Attempts at

    anchoring an implant by means of a regenerated

    fibrous tissue layer forming a simulated periodontal

    ligament have also been unsuccessful. It has been stated

    in bone reconstruction literature that direct anchorage

    to living bone of load-bearing implants does not work

    in the long run. Contrary to this concept, we now

    suggest that the edentulous jaw can be provided with

    jaw bone-anchored prostheses according to the princi-

    ple of osseointegration with good and predictable

    long-term prognosis.

    Orthopedic reconstructions that use nonbiologic

    prosthetic materials frequently rely on implant anchor-

    age by a space filler of so-called bone cement: methyl

    methacrylate. The induced surgical and chemical trau-

    ma results in death of osteocytes at the anchorage

    interface. After an initial period of adequate implant

    retention, the damaged bone becomes resorbed and the

    implant is subsequently kept in place only by low

    differentiated soft tissue, a kind of scar tissue.

    The implant is then separated from healthy bone by

    a soft tissue layer, which provides inadequate reten-

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    Fig. 7. Radiographs of main types of resorption anatomy in patients comprising our

    clinical material. A, Orthopantomogram showing advanced resorption. B, Profile

    radiogram showing extreme resorption. C, D, and E, Typical progressive bone loss in

    edentulous jaw at 5-year interval. F, Diagrammatic representation of lower jaw morphol-

    ogy corresponding to jaw bone topography represented in C and E, respectively.

    Fig. 8. Schematic representation of anchorage unit

    based on principle of screw-connected compo-

    nents: fixture, abutment, and center screw for

    prosthesis attachment. Apical part of titanium fix-

    ture is designed to cut and thread bottom of fix-

    ture site.

    tion as well as shielding of the surrounding bone from

    the load stimulus required for adequate bony remodel-

    ing and maintenance. This will also occur even if the

    preparation of the implant site provides adequate

    anatomic congruence between the geometry of the

    implant and the bone site since both surgical and

    immediate loading trauma will lead to the formation of

    a thin layer of connective tissue at the bone-implant

    interface. In a long-term context, such an interface

    constitutes a locus minoris resistentiae that allows

    small relative movements between implant and bone.

    This suggests a risk of inflammatory reactions and a

    propagation of bacteria and their products from the

    oral cavity to the anchorage region if the implant is

    connected to an abutment that pierces skin or mucous

    membrane. On the other hand, the osseointegrated

    implant is directly connected to living remodeling bone

    without any intermediate soft tissue component; there-

    fore, it provides directly transferred loads to the

    anchoring bone. The decisive problem is to allow bone

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    OSSEOINTEGRATION

    Fig. 9. A, Radiograph of a lower jaw fixture that, together with three other fixtures, has

    supported a full arch prosthesis for 17 years. B, Densitometric profile measured along

    dashed line (Kontron IBAS image analysis system, Munich, West Germany). An

    important feature is condensation of bone toward interface zone.

    2 1

    6 7

    C

    a

    Fig. 10. Diagrammatic representation of biology of osseointegration. A, Threaded bone

    site cannot be made perfectly congruent to implant. Object of making threaded socket in

    bone is to provide immobilization immediately after installation and during initial

    healing period. Diagram is based on relative dimensions of fixture and fixture site.

    2

    q

    = Contact between fixture and bone (immobilization); 2 = hematoma in closed cavity,

    bordered by fixture and bone; 3 = bone that was damaged by unavoidable thermal and

    mechanical trauma; 4 = original undamaged bone; and 5 = fixture. B, During unloaded

    healing period, hematoma becomes transformed into new bone through callus formation

    (6). 7 = Damaged bone, which also heals, undergoes revascularization, and de- and

    remineralization. C, After healing period, vital bone tissue is in close contact with fixture

    surface, without any other intermediate tissue. Border zone bone (8) remodels in

    response to masticatory load applied. D, In unsuccessful implants, nonmineralized

    connective tissue (9), constituting a kind of pseudoarthrosis, forms in border zone at

    implant. This development can be initiated by excessive preparation trauma, infection,

    loa.ding too early in the healing period before adequate mineralization and organization

    of .hard tissue has taken place, or supraliminal loading at any time, even many years after

    integration has been established. Osseointegration cannot be reconstituted. Connective

    tissue can become organized to a certain degree, but in our opinion it is not a proper

    anchoring tissue because of its inadequate mechanical and biologic capacities, which

    result in creation of a locus minoris resistentiae.

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    Fig.

    11.

    A, Successfully integrated lower jaw fixtures

    after 6 years of function. B, Fixture on left is not

    osseointegrated, although it is indirectly immobilized

    by prosthesis that is stabilized by remaining inte-

    grated fixtures.

    and marrow tissues to heal as such and not as low

    differentiated scar tissue.

    In order to create osseointegration, the preparation

    of the bone must be done so that minimal tissue injury

    is produced. In the handling of the edentulous jaw, it is

    important to recognize a few principles that are valid

    for all implant procedures. A minimal amount of

    remaining bone should be removed, and the basic

    topography of the region should not be changed. The

    retention of the original or transitional denture should

    be maintained during the healing period. If osseointe-

    gration is not obtained and the implant is removed or if

    for some other reason the patient wants to return to

    conventional denture wear, this should then function in

    the same way as before installation of the implants.

    Only one shape and dimension of implant should be

    required, and after 20 years of experimental and

    clinical development we have selected a screw-shaped

    implant made of pure titanium. Its dimensions of an

    outer diameter of 3.7 mm and a length of 10 mm allow

    its use in almost every edentulous jaw, regardless of the

    volume and topography of the remaining bone tissue

    (Fig. 8).

    Both prostheses and abutments are connected to the

    fixtures by screws so that the prostheses can be

    removed from the abutments and the abutment from

    the fixture for technical adjustments. The abutment

    can also be removed and the mucoperiosteum closed

    over the fixture for shorter periods of time or perma-

    nently. The existence of a titanium fixture in the jaw

    bone does not seem to cause adverse effects, and bone

    resorption arising from disuse atrophy appears to be

    reduced. If osseointegration is lost, the fixtures can be

    removed, with new bone formation observed in the

    implant site and preservation of the original jaw bone

    anatomy. In this way even if osseointegration is not

    achieved or maintained, the jaw bone is not destroyed

    or left with major defects.

    Healing time for bone tissue requires that fixtures

    implanted in carefully prepared sites in the jaw bone be

    left in situ without load bearing for a period of 3 to 6

    months. This period depends on the varying repair

    potential of the edentulous jaw bone. When abutments

    have been connected by the prosthesis, the jaw bone

    around the implant remodels over a period of 1 or more

    years until a steady state is reached. This state is

    characterized by negligible bone resorption and

    appears to be maintained. During the remodeling

    phase, some marginal bone is lost as a consequence of

    the installation surgical trauma and adaptation to the

    masticatory load (Fig. 9).

    Even with extreme care at the surgical preparation

    stage of the fixture site (Fig. lo), the bone at the

    interface is injured (A) and the required alignment at

    the 400 A level cannot be produced mechanically. It is

    provided by newly formed bone tissue (B), a biologic

    process that requires approximately 3 to 6 months.

    When a controlled load is applied to the bone through

    the implant, the bone remodels to an architecture

    related to the direction and magnitude of the load (C) .

    If the surgical trauma is too intense or if the load is

    applied too early or without proper control, osseointe-

    gration is not achieved

    (D),

    with a connective tissue

    anchorage resulting. Sometimes such a soft tissue layer

    is extremely thin: only a few microns wide. It may then

    provide a variable short-term anchorage, but in the

    long run the attachments prognosis becomes dubious.

    The soft tissue layer tends to increase in width;

    therefore, such a fixture should be removed and

    eventually replaced (Fig. 11).

    When osseointegration has been obtained and the

    fixtures are subjected to load-bearing under controlled

    conditions, the placement of the fixtures can be limited

    to the area between the mental foramina in the lower

    jaw and between the anterior sinus recesses in the

    upper jaw. Cantilevered extensions can be used so that

    an adequate replacement dentition can be provided.

    Fixtures can be positioned even distal to the sinus and

    mental foramen; but, because this is not required for

    the edentulous reconstruction per se and can actually

    cause clinical problems, it seems rational to restrict

    anchorage to these sites.

    A minimum of four fixtures appears to be adequate

    for support of a full arch prosthesis in the edentulous

    jaw (Fig. 12,

    A

    and B). However, if morphologically

    feasible, six fixtures are installed to provide a certain

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    OSSEOINTEGRATION

    Fig. 12. A and B, Diagrammatic and orthopantomographic representation of four

    osseointegrated fixtures supporting upper and lower full arch prostheses. Orthopanto-

    mogram shows topography of reconstruction after 6 years. C and D, If adequate space is

    available between maxillary sinuses or mandibular foramina, six fixtures are installed as

    support. E, This profile radiogram illustrates how prosthesis can be extended to provide

    an. adequate dentition even in molar region.

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    .O

    Fig. 13. Diagrammatic representation of jaw bone

    anatomy in a frontal sagittal section illustrates biome-

    chanical situation for implants in relation to various

    degrees of resorption of alveolar process. A, Normal

    anatomy as compared with extreme bone resorption

    prevailing in most of treated patients. B, In extreme

    resorption a very unfavorable leverage situation

    develops. This is due to distance between jaw bone

    and occlusal plane and to direction of implants that

    support prosthesis (see Fig. 12, E).

    reserve should a fixture not become integrated or lose

    its integration over the years (Fig. 12, C and D).

    While extremely careful surgical handling of the

    hard and soft tissues is required to achieve osseointe-

    gration of the implants, the maintenance of the osseoin-

    tegration relies on equally careful prosthodontic thera-

    py. Careful and frequent control and adjustment of

    occlusion are essential. The artificial teeth are made of

    acrylic resin, which tends to compensate for the resil-

    ience of the periodontium. Most of the edentulous

    patients treated by osseointegration present an extreme

    degree of alveolar bone resorption. The vertical dimen-

    sions of the tissue defect to be covered by the prosthesis

    demand particular skill and consideration in its design

    to ensure load bearing without mechanical failures and

    at the same time to make sure that phonetic and

    cosmetic requirements are met (Fig. 13).

    Clinical evidence for the lasting integration of pros-

    thesis-loaded fixtures has been obtained from osseoin-

    tegrated fixtures that were removed along with sur-

    rounding bone because of mechanical rather than

    biologic failures. Fig. 14 shows a typical example of a

    well-functioning integrated upper jaw fixture removed

    by trephine with surrounding bone after 6 years of

    clinical function. The bone could not be removed from

    the (integrated) fixtures without destroying the inter-

    face. Under the light microscope, the anatomic congru-

    ence of the anchoring bone to the geometry of the

    (scrutinized) fixture is illustrated; and, in scanning

    electron microscopy, processes of osteob lasts seem to

    grow on the titanium surface.

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    BRANEMARK

    Biopsies from the mucoperiosteum around the trans-

    epithelial abutment show a similar appearance of the

    soft tissue cells providing a seal toward the oral cavity.

    Biophysical and biochemical analyses of long-term

    experimental and clinical material indicate that there is

    in fact an active interchange between the implanted

    titanium fixture and the soft and hard tissues, which

    eventually results in improved anchorage over the

    years.

    OTHER APPLICATIONS

    Extraoral application of titanium fixtures has been

    used since 1976. A specially designed fixture has been

    used to anchor hearing aids for bone-conducting

    devices. It is placed behind the ear in patients with

    certain audiologic impairments. Similar fixtures have

    also been used as anchorage for auricular epitheses

    (maxillofacial prostheses). A special procedure for

    handling the skin and subcutaneous tissue relationship

    to the abutment enabled us to handle soft tissue

    problems, and all installed fixtures became and have

    remained integrated. Fifteen patients were supplied

    with this kind of bone-conducting hearing aid between

    1977 and 1982. Eighteen patients were provided with

    20 auricular epitheses attached to 78 fixtures between

    1979 and 1982. Using the same basic anchorage

    principle, we are now developing methods, for exam-

    ple, for tissue integration of epitheses that replace the

    orbital sections of the maxilla.

    Osseointegration has also been applied to long bones

    in the reconstruction of damaged or diseased oints. So

    far, osseointegrated fixtures have been used as anchor-

    age for joint prostheses in the metacarpophalangeal

    joints. There seems to be two advantages with the

    osseointegrated joint prosthesis: (1) direct anchorage to

    living remodeling bone provides important mechanical

    stability for the function of the joint and the hand and

    (2) the mechanical components constituting the joint

    itself are facultatively removable from the fixtures.

    Therefore, a replacement joint mechanism can easily

    be installed in the future as a result of wear of

    components, or if a better design or material becomes

    available.

    Work is now in progress to explore the possible

    value of osseointegrated joint prostheses in the distal

    radioulnar joint and in the elbow joint as well as in

    joint replacement in the lower extremity, particularly

    the knee and the hip joints.

    Finally, preliminary studies have been performed on

    the attachment of prosthetic substitutes for lost fingers,

    hands, and arms and lower legs to osseointegrated

    fixtures by means of skin-penetrating abutments as the

    method of connection.

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    OSSEOINTEGRATION

    Fig. 14. A, Upper jaw fixtures with surrounding bone removed because of failure of

    mechanical components after 6 years of function with persisting integration. Specimen

    was removed by a trephine and cut longitudinally into two halves with a diamond disk.

    B, In light microscopy, bone threads of fixture site are clearly defined. C, High-

    resolution scanning electron micrograph of an osteoblast with its cellular processes

    adapted to surface of fixture shown in A.

    In conclusion , I have attempted to present an over-

    view of the conceptual development and the experi-

    mental and clinical application of osseointegration. Its

    long-term clinical dental application has already been

    demonstrated and documented in Sweden. I hope that

    my material will provoke and catalyze similar experi-

    mental work and clinical application elsewhere.

    REFERENCES

    A reference list enumerating the relevant research

    referred to in this overview is available from the author

    under the following headings:

    1. Blood as a mobile tissue and studies on intravas-

    cular rheology of blood

    2. Vital microscopy techniques

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    3. Microvascular structure and

    and diseased conditions

    4. Tissue injury and repair

    function in normal

    5. Tissue-integrated prostheses in oral and craniofa-

    cial reconstruction

    6. Immediate and preformed autologous grafts

    7. Bone, marrow, joint, and tendon anatomy, physi-

    ology, and pathophysiology

    For the list of references, write:

    Prof. P-I. Brinemark

    Institute for Applied Biotechnology

    Box 33053

    S-400 33 Gijteborg

    Sweden

    410

    The invaluable assistance of the late Viktor Kuikka is acknowl-

    edged. He helped design and develop the mechanical components

    used for anchorage as well as the surgical instruments.

    Reprint requests to:

    DR. GEORGEA. ZARB

    UNIVERXR OF TORONTO

    FACULTY OF DENTISTRY

    124 EDWARDST.

    TORONTO, ONT. M5G lG6

    CANADA

    SEPTEMBER 1983

    VOLUME 50

    NUMBER 3